11β-HSD-1 is an enzyme that converts inactive steroids, 11β-dehydrosteroid into its active steroids and is considered to be important in the basal metabolic rate in the living body (Non-patent Document 1). Moreover, 11β-HSD-1 knockout mice have the resistance to hyperglycemia induced by obesity and stress (Non-patent Document 2). In addition, a similar phenomenon was observed in human on administration of 11β-HSD-1 inhibitor, carbenoxolone (Non-patent Document 3). These facts suggest that the 11β-HSD-1 inhibitors could be useful as drugs for the treatment of insulin independent diabetes and obesity (Non-patent Document 4).
Patent Document 1 describes that hetero ring derivatives are useful as kinase inhibitors for the treatment of cancer, Alzheimer's disease, viral infections and autoimmune disease, but does not describe the inhibitory activity to the type 11β hydroxysteroid dehydrogenase.
The compounds having an isoxazole group have been described in Patent Document 2 as a useful compound for the treatment of hypertension as well as inflammation and the structure of them are limited to that without substituent at 4-position on an isoxazole group, and no compounds having the substituent on an isoxazole group such as the present compound have not been described.
Patent Document 3 to 6 disclose various compounds that have the inhibitory activity to 11β hydroxysteroid dehydrogenase type 1.
Patent Document 3 and 4 mainly disclose the compounds having a phenyl group, and does not disclose the compounds having an isoxazole group described in the present invention.
Patent Document 5 does not disclose the compounds having an isoxazole group described in the present invention.
Patent Document 6 describes the compounds having a pyrazole group. The substituent at 4 position on the pyrazole group is hydrogen, halogen or optionally substituted alkyl (the substituent is hydroxyl or fluorine). The above document does not disclose the compounds having a cyclohexyl group described in the present invention.    [Patent Document 1] WO03/013517    [Patent Document 2] U.S. Pat. No. 4,562,187    [Patent Document 3] WO04/056744    [Patent Document 4] WO04/056745    [Patent Document 5] WO04/065351    [Patent Document 6] WO05/016877    [Non-patent Document 1] Clin. Endocrinol, 1996, 44, 493    [Non-patent Document 2] Proc. Nat. Acad. Sci. USA, 1997, 94, 14924    [Non-patent Document 3] J. Clin. Endocrinol. Metab., 1995, 80, 3155    [Non-patent Document 4] Lancet, 1997, 349, 1210